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Mechanisms involved in enhancement of osteoclast formation and function by low molecular weight hyaluronic acid.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2005 May 13; Vol. 280 (19), pp. 18967-72. Date of Electronic Publication: 2005 Mar 09. - Publication Year :
- 2005
-
Abstract
- Hyaluronic acid (HA) is a component of the extracellular matrix that has been shown to play an important role in bone formation, resorption, and mineralization both in vivo and in vitro. We examined the effects of HA at several molecular weights on osteoclast formation and function induced by RANKL (receptor activator of NF-kappa B ligand) in a mouse monocyte cell line (RAW 264.7). HA at M(r) < 8,000 (low molecular weight HA (LMW-HA)) enhanced tartrate-resistant acid phosphatase-positive multinucleated cell formation and tartrate-resistant acid phosphatase activity induced by RANKL in a dose-dependent manner, whereas HA at M(r) > 900,000 (high molecular weight HA (HMW-HA)) showed no effect on osteoclast differentiation. LMW-HA enhanced pit formation induced by RAW 264.7 cells, whereas HMW-HA did not, and LMW-HA stimulated the expression of RANK (receptor activator of NF-kappa B) protein in RAW 264.7 cells. In addition, we found that LMW-HA enhanced the levels of c-Src protein and phosphorylation of ERKs and p38 MAPK in RAW 264.7 cells stimulated with RANKL, whereas the p38 MAPK inhibitor SB203580 inhibited RANKL-induced osteoclast differentiation. This enhancement of c-Src and RANK proteins induced by LMW-HA was inhibited by CD44 function-blocking monoclonal antibody. These results indicate that LMW-HA plays an important role in osteoclast differentiation and function through the interaction of RANKL and RANK.
- Subjects :
- Acid Phosphatase pharmacology
Animals
Antibodies, Monoclonal metabolism
Blotting, Western
Bone Resorption
CSK Tyrosine-Protein Kinase
Carrier Proteins metabolism
Cell Differentiation
Cell Line
Cell Survival
Dose-Response Relationship, Drug
Enzyme Inhibitors pharmacology
Extracellular Matrix metabolism
Hyaluronan Receptors biosynthesis
Imidazoles pharmacology
Isoenzymes pharmacology
Membrane Glycoproteins metabolism
Mice
Molecular Weight
Monocytes metabolism
Osteoclasts drug effects
Phosphorylation
Protein-Tyrosine Kinases metabolism
Pyridines pharmacology
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
Signal Transduction
Tartrate-Resistant Acid Phosphatase
Time Factors
Up-Regulation
p38 Mitogen-Activated Protein Kinases metabolism
src-Family Kinases
Hyaluronic Acid pharmacology
Osteoclasts metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 280
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 15757905
- Full Text :
- https://doi.org/10.1074/jbc.M412740200